Monoamine Oxidase Activity and Localisation in the Brain and the Activity in Relation to Psychiatric Disorders1

Oreland, L.; Arai, Yasuhiko; Stenström, Anders; Fowler, Christopher J.

doi:10.1159/000407521

Cited by 48 publications

(15 citation statements)

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“…The ability of glial cells to metabolize monoamine neurotransmitters has been firmly established; in fact, more than 90% of brain MAO is found extraneuronally (Oreland et al, 1983). MAO B is abundant in glial cells (Shih et al, 1999), and the interaction between glucocorticoids and MAO B has also been well defined in the glial culture system (Carlo et al, 1996).…”

Section: Resultsmentioning

confidence: 99%

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

Chen

Ou²,

Wu³

et al. 2010

Mol Pharmacol

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Glucocorticoid steroid hormones play important roles in many neurophysiological processes such as responses to stress, behavioral adaption, and mood. One mechanism by which glucocorticoids exert functions in the brain is via the modulation of neurotransmission systems. Glucocorticoids are capable of inducing the activities of monoamine oxidases (MAOs), which degrade monoamine neurotransmitters including serotonin, norepinephrine, phenylethylamine, and dopamine. However, the molecular mechanisms for such induction are not yet fully understood. Here, we report that dexamethasone, a synthetic glucocorticoid hormone, stimulates MAO B (an isoform of MAOs) promoter and catalytic activities via both the fourth glucocorticoid response element (GRE) and simian virus 40 promoter factor 1 (Sp1) binding sites in MAO B promoter. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analysis demonstrated that glucocorticoid receptor binds to the fourth GRE in vitro and in vivo. Using Sp1-binding motifs as bait in a yeast one-hybrid system, we identified two novel transcriptional repressors of MAO B, E2F-associated phosphoprotein (EAPP) and R1 (RAM2/CDCA7L/ JPO2), that down-regulate MAO B via MAO B core promoter, which contains Sp1 sites. EMSA suggested that EAPP and R1 competed with Sp1 for binding to the Sp1 site in vitro. Moreover, EAPP and R1 reduced Sp1-activated glucocorticoid activation of MAO B promoter. In response to dexamethasone, lower occupancy by EAPP and R1 and higher occupancy by Sp1 were shown at the natural MAO B core promoter. Together, this study uncovers for the first time the molecular mechanisms for glucocorticoid activation of MAO B gene and provides new insights into the hormonal regulation of MAO.

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Section: Resultsmentioning

confidence: 99%

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

Chen

Ou²,

Wu³

et al. 2010

Mol Pharmacol

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“…Ratios of between 2.5 and 3 were estimated for the thalamus-to-cerebellum and basal-gangliato-cerebellum ratios based on data from Fowler et al (1980), Glover et al (1980), andOreland et al (1983). Values for MAO A appear to be in the same range.…”

Section: Discussionmentioning

confidence: 99%

Strategy for the Formation of Parametric Images under Conditions of Low Injected Radioactivity Applied to PET Studies with the Irreversible Monoamine Oxidase a Tracers [¹¹C]Clorgyline and Deuterium-Substituted [¹¹C]Clorgyline

Logan

Fowler

Ding

et al. 2002

J Cereb Blood Flow Metab

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Summary:The construction of parametric positron emission tomography images of enzyme or receptor concentration obtained using irreversibly binding radiotracers presents problems not usually encountered with reversibly binding radiotracers. Difficulties are most apparent in brain regions having low blood flow and/or high enzyme or receptor concentration and are exacerbated with noisy data. This is especially true when minimal doses of radiotracer are administered. A comparison was recently reported of the irreversible monoamine oxidase A (MAO A) radiotracers [ 11 C]clorgyline (CLG) and deuteriumsubstituted [11 C]clorgyline (CLG-D) in the human brain using region of interest (ROI) analysis in which the authors observed an unexpected loss of image contrast with CLG-D compared with CLG. In order to more fully investigate patterns of binding of these irreversibly binding radiotracers, a strategy was devised to reduce noise in the generation of parametric images of the model term related to enzyme or receptor concentration. The generalized linear least squares (GLLS) method of Feng et al. (1995), a rapid linear method that is unbiased, was used for image-wide parameter estimation. Since GLLS can fail in the presence of large amounts of noise, local voxels were grouped within the image to increase the signal, and the GLLS method was combined with the standard nonlinear estimation methods when necessary. Voxels were grouped together depending on their proximity and whether they fell within a specified range of the time-integrated image. It was assumed that voxels meeting both criteria are functionally related. Simulations reflecting varying enzyme concentrations were performed to assess precision and accuracy of parameter estimates in the presence of varying amounts of noise. Using this approach, images were generated of the combination parameter k 3 ( ‫ס‬ K 1 / k 2 , where K 1 and k 2 are plasma-to-tissue and tissue-to-plasma transport constants, respectively) that is related to enzyme concentration as well as images of the transport constant K 1 for individual subjects. Reasonably high-quality images of both K 1 and k 3 were obtained for CLG and CLG-D for individual subjects even with low injected doses averaging 6 mCi. While there were no differences in the K 1 images, the k 3 images revealed the loss of contrast previously reported for CLG-D using the ROI analysis. This method should be generalizable to other tracers and should facilitate the analysis of group differences.

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“…MAO A has been reported to be relatively high in thalamus (29,30) and in occipital cortex (31), with intermediate values in basal ganglia, frontal, and temporal cortices (29,32) and a low concentration in cerebellum (31), though this comparison is limited by the lack of a single postmortem study measuring the same regions sampled by PET.…”

Section: Discussionmentioning

confidence: 99%

Brain monoamine oxidase A inhibition in cigarette smokers

Fowler

Volkow

Wang

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

388

219

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Several studies have documented a strong association between smoking and depression. Because cigarette smoke has been reported to inhibit monoamine oxidase (MAO) A in vitro and in animals and because MAO A inhibitors are effective antidepressants, we tested the hypothesis that MAO A would be reduced in the brain of cigarette smokers. We compared brain MAO A in 15 nonsmokers and 16 current smokers with [ 11 C]clorgyline and positron emission tomography (PET). Four of the nonsmokers were also treated with the antidepressant MAO inhibitor drug, tranylcypromine (10 mg͞day for 3 days) after the baseline PET scan and then rescanned to assess the sensitivity of [ 11 C]clorgyline binding to MAO inhibition. MAO A levels were quantified by using the model term k 3 which is a function of brain MAO A concentration. Smokers had significantly lower brain MAO A than nonsmokers in all brain regions examined (average reduction, 28%). The mean k 3 values for the whole brain were 0.18 ؎ 0.04 and 0.13 ؎ 0.03 cc brain (ml plasma )؊1 min ؊1 for nonsmokers and smokers, respectively; P < 0.0003). Tranylcypromine treatment reduced k 3 by an average of 58% for the different brain regions. Our results show that tobacco smoke exposure is associated with a marked reduction in brain MAO A, and this reduction is about half of that produced by a brief treatment with tranylcypromine. This suggests that MAO A inhibition needs to be considered as a potential contributing variable in the high rate of smoking in depression and in the development of more effective strategies for smoking cessation.There are approximately 1 billion cigarette smokers in the world today and about 3 million die each year from smokingassociated illnesses (1). This places a sense of urgency on understanding the neuropharmacological properties of tobacco smoke and their relationship to smoking behavior and epidemiology. For example, it is not understood why smoking is more prevalent in depression and why smoking cessation is less successful in depressed patients (2, 3). Though it is unlikely that any one factor accounts for the strong association between smoking and depression, it is possible that tobacco smoke may have antidepressant properties. One of the molecular targets proposed to link smoking and depression is monoamine oxidase (MAO) (4, 5), an enzyme which was first associated with mood over 40 years ago when it was discovered that MAO inhibitors had antidepressant properties (6, 7).MAO exists in two subtypes (MAO A and B) that are different gene products (8, 9). In the brain, MAO A oxidizes serotonin and norepinephrine and is found primarily in catecholaminergic neurons, whereas MAO B oxidizes benzylamine and phenethylamine and is localized in serotonergic neurons and in glial cells (10). Both forms oxidize dopamine (11). The antidepressant effects of the nonselective MAO inhibitors are generally attributed to the inhibition of MAO A (12).We recently reported that smokers have reduced brain MAO B relative to nonsmokers and former smokers (13).Others have fo...

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Monoamine Oxidase Activity and Localisation in the Brain and the Activity in Relation to Psychiatric Disorders1

Cited by 48 publications

References 0 publications

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

Strategy for the Formation of Parametric Images under Conditions of Low Injected Radioactivity Applied to PET Studies with the Irreversible Monoamine Oxidase a Tracers [¹¹C]Clorgyline and Deuterium-Substituted [¹¹C]Clorgyline

Brain monoamine oxidase A inhibition in cigarette smokers

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Monoamine Oxidase Activity and Localisation in the Brain and the Activity in Relation to Psychiatric Disorders1

Cited by 48 publications

References 0 publications

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

Transcription Factor E2F-Associated Phosphoprotein (EAPP), RAM2/CDCA7L/JPO2 (R1), and Simian Virus 40 Promoter Factor 1 (Sp1) Cooperatively Regulate Glucocorticoid Activation of Monoamine Oxidase B

Strategy for the Formation of Parametric Images under Conditions of Low Injected Radioactivity Applied to PET Studies with the Irreversible Monoamine Oxidase a Tracers [11C]Clorgyline and Deuterium-Substituted [11C]Clorgyline

Brain monoamine oxidase A inhibition in cigarette smokers

Contact Info

Product

Resources

About

Strategy for the Formation of Parametric Images under Conditions of Low Injected Radioactivity Applied to PET Studies with the Irreversible Monoamine Oxidase a Tracers [¹¹C]Clorgyline and Deuterium-Substituted [¹¹C]Clorgyline